1. Field of the Invention
This invention relates to the preparation of 3,3-dimethylbutyraldehyde. More particularly, the invention relates to the preparation of 3,3-dimethylbutyraldehyde by the reduction of 3,3-dimethylbutyric acid.
2. Description of the Background Art
U.S. Pat. No. 5,480,668 to Nofre et al. describes high potency sweetening agents comprising N-substituted derivatives of aspartame (L-aspartyl-L-phenylalanine methyl ester). A preferred compound described by Nofre is N-[N-(3,3-dimethylbutyl)-L-α-aspartyl]-L-phenylalanine 1-methyl ester, also known as neotame. The '668 patent describes the production of this compound by the reaction of 3,3-dimethylbutyraldehyde with aspartame in the presence of a reducing agent. Other synthesis methods for the production of neotame also use 3,3-dimethylbutyraldehyde, for example, U.S. Pat. No. 5,728,862 to Prakash.
As 3,3-dimethylbutyraldehyde has not been utilized in commercial quantities, conventional methods for its production have been limited, resulting in its availability only in limited quantities and at very high prices. Recently, a number of processes for the production of 3,3-dimethylbutyraldehyde have been discovered, including processes described in U.S. Pat. No. 5,770,775 to Prakash et al., U.S. Pat. No. 5,973,209 to Prakash et al., U.S. Pat. No. 5,856,584 to Prakash et al., U.S. Pat. No. 5,905,175 to Prakash et al., U.S. Pat. No. 5,994,593 to Prakash et al., and U.S. Pat. No. 5,977,415 to Prakash et al. Each of these processes produces 3,3-dimethylbutyraldehyde having acceptable purity and yields; however, the cost of such processes is such that further cost reductions remain desirable. 3,3-dimethylbutyraldehyde is also prepared by the reduction of 3,3-dimethylbutyric acid by lithium and methyl amine (Bock, et al. J. Am. Chem. Soc. 1974, 96, 2814) and by the Rosenmund reduction of tert-butylacetyl chloride (Collect. Czech. Chem. Commun. 1987, 52, 514). Recently the synthesis of aldehyde by the reduction of acid has been reported in WO 01/38297 using hydrogen, palladium acetate and tri p-tolylphosphine; however, the synthesis of 3,3-dimethylbutyraldehyde from 3,3-dimethylbutyric acid (tert-butylacetic acid) is not described therein.
The synthesis of 3,3-dimethylbutyric acid has been reported, for example, Japanese Patent JP 02-006429 discloses the reaction of isobutylene with vinylidene dichloride and sulfuric acid, followed by hydrolysis. However, this process would have significant cost constraints that would limit its applicability for use as an intermediate for products such as 3,3-dimethylbutyraldehyde.
Thus, there remains a need for a process to produce commercial quantities of 3,3-dimethylbutyraldehyde having acceptable purity and yields, as well as a reduced cost. The present invention provides such a process.